This project examines the physiological effects and the underlying biochemical mechanisms of the action of delta opioid peptide DADLE and a DADLE-related protein HIT (Hibernation Induction Trigger) in tissue survival. In this fiscal year, we found that both DADLE and HIT display similar biological activity in mouse vas deferens bioassay. Further, we have partially sequenced an alpha-1-glycoprotein-like 88 kDa hibernation-related protein in HIT, which may prove to be the blood- borne HIT molecule. The delta opioid peptide DADLE is also found to reverse the pre-existing neuronal damage induced by methamphetamine (METH). Specifically, a single injection of METH causes a long-term loss of dopamine transporters (DAT) in the striatum of CD-1 mouse. Two week after the injection of METH, 60% of DAT was destroyed. A single injection of DADLE, given at day 14 post METH administration, restores the DAT level close to that of controls at day 16. In a separate study examining the genomic effect exerted by METH in CD-1 mice, we found that the elevated level of the mRNA of an immediate early gene, c-fos, is alleviated by a DADLE pretreatment. Thus, our results indicate that DADLE can promote the neuronal survival against pre-existing insults and that this action of DADLE may involve influences at the genomic level. - opioid; myocardiac survival; ischemia; methamphetamine; neurotoxicity; hibernation induction protein; hibernation.